SPARC Induces E-Cadherin Repression and Enhances Cell Migration through Integrin αvβ3 and the Transcription Factor ZEB1 in Prostate Cancer Cells
Abstract
:1. Introduction
2. Results
2.1. SPARC Downregulates E-Cadherin and Enhances ZEB1 and Vimentin Expression in PCa Cell Lines
2.2. SPARC Increases the Expression of Integrin β3 Subunit and Requires Its Activity to Inhibit E-Cadherin
2.3. Silencing of SPARC Decreases the Phosphorylation of FAK-Y925 and Impairs Focal Adhesion Formation
2.4. Integrin αvβ3 Activation and ZEB1 Expression Are Required for SPARC-Induced E-Cadherin Downregulation and Enhanced Migration
3. Discussion
4. Materials and Methods
4.1. Cell Lines
4.2. Lentiviral Transduction
4.3. Protein and Peptides
4.4. Western Blot
4.5. Indirect Immunofluorescence
4.6. RNA Extraction and RT-qPCR
4.7. Focal Adhesion Formation Assay
4.8. Transwell Migration Assay
4.9. Wound Healing Assay
4.10. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
EMT | Epithelial–mesenchymal transition |
FAK | Focal adhesion kinase |
ILK | Integrin-linked kinase |
PCa | Prostate cancer |
RAC1 | Rac Family Small GTPase 1 |
RHOA | Ras Homolog Family Member A |
shSPARC | Short hairpin RNAs against SPARC |
shScramble | Short hairpin RNA of scrambled sequence |
shZEB1 | Short hairpin RNAs against ZEB1 |
Slug | Zinc finger protein SNAI2 |
Snail | Zinc finger protein SNAI1 |
SPARC | Secreted protein acidic and rich in cysteine |
SPARC_HA | Ectopic SPARC expression by lentiviral transduction |
ZEB1 | Zinc finger E-box-binding homeobox 1 |
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Antibody | Brand | Catalogue | Dilution |
---|---|---|---|
SPARC | Cell Signaling | 5420 | 1:1000 |
ZEB1 | eBioscience | 14974182 | 1:1000 |
E-cadherin | BD Transduction Laboratories | 610181 | 1:1000 |
Vimentin | AbCam | Ab8978 | 1:2000 |
Integrin β1 | Cell Signaling | 9669T | 1:1000 |
Integrin β3 | Cell Signaling | 13166T | 1:1000 |
Integrin β4 | Cell Signaling | 14803T | 1:1000 |
Integrin β5 | Cell Signaling | 3629T | 1:1000 |
Integrin α5 | Cell Signaling | 4705T | 1:1000 |
Integrin αv | Cell Signaling | 4711T | 1:1000 |
FAK | Cell Signaling | 13009T | 1:1000 |
P-FAK (Y397) | Cell Signaling | 8556T | 1:1000 |
P-FAK (Y576/577) | Cell Signaling | 3281T | 1:1000 |
P-FAK (Y925) | Cell Signaling | 3284T | 1:1000 |
Actin | MP Biomedicals | 691002 | 1:5000 |
Goat anti-Rabbit IgG HRP | Jackson Immunoresearch | 111-035-003 | 1:10,000 |
Goat anti-Mouse IgG HRP | Jackson Immunoresearch | 115-035-003 | 1:10,000 |
Antibody | Brand | Catalogue | Dilution |
---|---|---|---|
Vinculin | Sigma-Aldrich | V9131 | 1:400 |
Donkey anti-Rabbit IgG Alexa Fluor 594 | Life Technologies | A21207 | 1:500 |
Goat anti-Mouse IgG Alexa Fluor 555 | AbCam | ab150118 | 1:500 |
Gen Name | Forward Primer | Reverse Primer |
---|---|---|
Secreted Protein Acidic and Rich in Cysteine (SPARC) | 5′-AAC CGA AGA GGA GGT GGT-3′ | 5′-GCA AAG AAG TGG CAG GAA GA-3′ |
Cadherin 1 (E-Cadherin) | 5′-GAA CGC ATT GCC ACA TAC AC-3′ | 5′-ATT CGG GCT TGT TGT CAT TC-3′ |
Vimentin | 5′-GCC AAG GCA AGT CGC G-3′ | 5′-CAT TTC ACG CAT CTG GCG-3′ |
Zinc Finger E-Box Binding Homeobox 1 (ZEB1) | 5′-TTC ACA GTG GAG AGA AGC CA-3′ | 5′-GCC TGG TGA TGC TGA AAG AG-3′ |
Integrin Subunit Alpha V | 5′-TCT CTC GGG ACT CCT GCT AC-3′ | 5′-CTG GGT GGT GTT TGC TTT GG-3′ |
Integrin Subunit Beta 3 | 5′-ACC AGT AAC CTG CGG ATT GG-3′ | 5′-CTC ATT GAA GCG GGT CAC CT-3′ |
Rac Family Small GTPase 1 (RAC1) | 5′-TCC GCA AAC AGA TGT GTT CTT A-3′ | 5′-ATG GGA GTG TTG GGA CAG TG-3′ |
Ras Homolog Family Member A (RHOA) | 5′-GGT GAT GGA GCC TGT GGA AA-3′ | 5′-TGT GTC CCA CAA AGC CAA CT-3′ |
Protein Tyrosine Kinase 2 (Focal adhesion kinase; FAK) | 5′-CAG GGT CCG ATT GGA AAC CA-3′ | 5′-CTG AAG CTT GAC ACC CTC GT-3′ |
Integrin Linked Kinase (ILK) | 5′-CTT CCC TGG ATC ACT CCA CAG-3′ | 5′-GGG AGA AGC CAT GAT CGT CC-3′ |
Pumilio RNA Binding Family Member 1 (PUM1) | 5′-CGG TCG TCC TGA GGA TAA AA-3′ | 5′-CGT ACG TGA GGC GTG AGT AA-3’ |
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López-Moncada, F.; Torres, M.J.; Lavanderos, B.; Cerda, O.; Castellón, E.A.; Contreras, H.R. SPARC Induces E-Cadherin Repression and Enhances Cell Migration through Integrin αvβ3 and the Transcription Factor ZEB1 in Prostate Cancer Cells. Int. J. Mol. Sci. 2022, 23, 5874. https://doi.org/10.3390/ijms23115874
López-Moncada F, Torres MJ, Lavanderos B, Cerda O, Castellón EA, Contreras HR. SPARC Induces E-Cadherin Repression and Enhances Cell Migration through Integrin αvβ3 and the Transcription Factor ZEB1 in Prostate Cancer Cells. International Journal of Molecular Sciences. 2022; 23(11):5874. https://doi.org/10.3390/ijms23115874
Chicago/Turabian StyleLópez-Moncada, Fernanda, María José Torres, Boris Lavanderos, Oscar Cerda, Enrique A. Castellón, and Héctor R. Contreras. 2022. "SPARC Induces E-Cadherin Repression and Enhances Cell Migration through Integrin αvβ3 and the Transcription Factor ZEB1 in Prostate Cancer Cells" International Journal of Molecular Sciences 23, no. 11: 5874. https://doi.org/10.3390/ijms23115874